RESUMO
Progressive multifocal leukoencephalopathy (PML) is an opportunistic central nervous system infection caused by the human polyomavirus 2, leading to demyelination from oligodendrocyte death and rapid neurologic decline. Most commonly, PML affects patients in immunocompromised states. However, rare reports of PML in an immunocompetent host exist. Here, we report two cases of PML in older individuals with chronic kidney disease (CKD). CKD can ultimately lead to immune system dysfunction and place patients in a relatively immunosuppressed state. Testing for JC virus should remain a consideration for rapid, unexplained neurologic decline even without known immunocompromised status in the appropriate clinical setting.
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Vírus JC , Leucoencefalopatia Multifocal Progressiva , Insuficiência Renal Crônica , Humanos , Idoso , Leucoencefalopatia Multifocal Progressiva/complicações , Vírus JC/fisiologia , Hospedeiro Imunocomprometido , Insuficiência Renal Crônica/complicaçõesRESUMO
PURPOSE OF REVIEW: One of the major concerns in global health is the deteriorating control of dyslipidemia (DLD), which is a very strong modifiable risk factor for untoward cardiovascular disease (CVD) outcomes. It serves as a foundation for atherosclerotic lesions that can be destabilized by co-inflammatory processes leading to distal clot migration and other related CVD events. There are many misconceptions regarding the management of DLD. Many health sectors advocate for weight loss without a clear-cut target to achieve better CVD outcomes. There is growing evidence that exercise training compliance regardless of weight change is a more reliable indicator of favorable outcomes. This review is intended to understand the relationship between exercise training, lipoprotein readings, and with CVD and all-cause morbidity and mortality. RECENT FINDINGS: Aerobic exercise training (aET) and resistance exercise training (rET) increase cardiorespiratory fitness (CRF) and muscular strength (MusS), respectively. Regardless of weight loss, aET and rET are both known to independently reduce mortality possibly partly through improvement of lipid profiles. Of the two modes of exercise, rET has propensity for enhanced compliance because of its significant lipid and mortality-attenuating effect even with just brief exercise sessions. However, there are several studies showing that participation in both modes of exercise causes more pronounced improvements in DLD and CVD-related mortality compared with either mode of exercise training alone. In addition, Lipoprotein-a [Lp(a)] has been increasingly acknowledged to be atherogenic because of its LDL core. The close proximity of Lp(a) with macrophages triggers the development of atheromas, plaque formation, and growth. This causes a cascade of inflammatory processes that increase the development of ischemic CVD and calcific aortic valve stenosis. Although exercise training is known to reduce plasma LDL-C levels, it has no direct effect on Lp(a) levels as the latter lipoprotein is not influenced by motion nor exercise. Reviews of multiple studies lead us to infer that exercise training may potentially have an indirect impact on Lp(a) attenuation because of the ability of exercise training to inhibit Proprotein Convertase Subtisilin/Kexin type-9 (PCSK-9), as some studies using pharmacologic therapy with PCSK-9 inhibitors were able to show a concomitant decrease in Lp(a) levels. SUMMARY: It is clear that normal-to-overweight populations who are highly active have better CVD outcomes and lipid profiles than their sedentary counterparts, and those who were underweight and unfit fared much worse. This allows us to take a more precise approach in the management of DLD rather than plainly focusing on gross weight in patients. Exercise training certainly has beneficial impact on longevity owing to its advantageous effect on lipoprotein levels and particle size. As such, reputable health societies, such as the ESC, ACC, and AHA have prescribed the ideal exercise training regimen, which have noticeable similarities. Increasing the use of wearable devices may help improve our ability to prescribe, quantify, and precisely track physical activity in our continuing efforts to combat increasing morbidity related to unhealthy lifestyles and inactivity.
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Aterosclerose , Doenças Cardiovasculares , Humanos , Exercício Físico , Lipoproteína(a) , Redução de PesoRESUMO
Background: There is a striking geographic variation in drug overdose deaths without a specific drug recorded, many of which likely involve opioids. Knowledge of the reasons underlying this variation is limited.Objectives: We sought to understand the role of medicolegal death investigation (MDI) systems in unclassified drug overdose mortality.Methods: This is an observational study of 2014 and 2018 fatal drug overdoses and U.S. county-level MDI system type (coroner vs medical examiner). Mortality data are from the CDC's National Center for Health Statistics. We estimated multivariable logistic regressions to quantify associations between MDI system type and several outcome variables: whether the drug overdose was unclassified and whether involvement of any opioid, synthetic opioid, methadone, and heroin was recorded (vs unclassified), for 2014 (N = 46,996) and 2018 (N = 67,359).Results: In 2018, drug overdose deaths occurring in coroner counties were almost four times more likely to be unclassified (OR 3.87, 95% CI 2.32, 6.46) compared to medical examiner counties. These odds ratios are twice as large as in 2014 (difference statistically significant, P < .001), indicating that medical examiner counties are improving identification of opioids in drug overdoses faster than coroner counties.Conclusions: Accurate reporting of drug overdose deaths depends on MDI systems. When developing state policies and local interventions aimed to decrease opioid overdose mortality, decision-makers should understand the role their MDI system is playing in underestimating the extent of the opioid overdose crisis. Improvements to state and county MDI systems are desirable if accurate reporting and appropriate policy response are to be achieved.
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Overdose de Drogas , Overdose de Opiáceos , Analgésicos Opioides , Médicos Legistas , Overdose de Drogas/epidemiologia , Heroína , Humanos , MetadonaRESUMO
PURPOSE OF REVIEW: In this article, we review the most current evidence for initiation and maintenance of various antihypertension (HTN) drug classes, including other misconceptions with respect to common comorbidities in patients with HTN. RECENT FINDINGS: Although the currently available anti-HTN agents have broad applicability in treating HTN, additional agents, such as angiotensin receptor-neprilysin inhibitors and novel nonsteroidal mineralocorticoid antagonists, have recently gained clinical significance. In addition, there have been some anecdotal concerns regarding the adverse effects, indications, and risks of COVID-19 infection/mortality when using certain anti-HTN agents. SUMMARY: Current guidelines currently address the treatment of primary HTN. However, isolated HTN is uncommon and often involves comorbid diseases that require specific regimentation. Several experimental medications are currently in late-stage trials showing potential superiority over current drugs that are available in the market.
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COVID-19 , Hipertensão , Anti-Hipertensivos/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Antagonistas de Receptores de Mineralocorticoides , SARS-CoV-2RESUMO
OBJECTIVE: To describe the spectrum of neurological complications observed in a hospital-based cohort of COVID-19 patients who required a neurological assessment. METHODS: We conducted an observational, monocentric, prospective study of patients with a COVID-19 diagnosis hospitalized during the 3-month period of the first wave of the COVID-19 pandemic in a tertiary hospital in Madrid (Spain). We describe the neurological diagnoses that arose after the onset of COVID-19 symptoms. These diagnoses could be divided into different groups. RESULTS: Only 71 (2.6%) of 2750 hospitalized patients suffered at least one neurological complication (77 different neurological diagnoses in total) during the timeframe of the study. The most common diagnoses were neuromuscular disorders (33.7%), cerebrovascular diseases (CVDs) (27.3%), acute encephalopathy (19.4%), seizures (7.8%), and miscellanea (11.6%) comprising hiccups, myoclonic tremor, Horner syndrome and transverse myelitis. CVDs and encephalopathy were common in the early phase of the COVID-19 pandemic compared to neuromuscular disorders, which usually appeared later on (p = 0.005). Cerebrospinal fluid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction was negative in 15/15 samples. The mortality was higher in the CVD group (38.1% vs. 8.9%; p = 0.05). CONCLUSIONS: The prevalence of neurological complications is low in patients hospitalized for COVID-19. Different mechanisms appear to be involved in these complications, and there was no evidence of direct invasion of the nervous system in our cohort. Some of the neurological complications can be classified into early and late neurological complications of COVID-19, as they occurred at different times following the onset of COVID-19 symptoms.
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COVID-19 , Doenças do Sistema Nervoso , Neurologia , Teste para COVID-19 , Humanos , Doenças do Sistema Nervoso/epidemiologia , Pandemias , Estudos Prospectivos , Sistema de Registros , SARS-CoV-2RESUMO
PURPOSE: The ultrasonographic and hemodynamic features of patients with carotid near-occlusion (CNO) are still not well known. Our aim was to describe the ultrasonographic and hemodynamic characteristics of a cohort of patients with CNO. METHODS: A prospective, observational, nationwide, and multicenter study was conducted from January/2010 to May/2016. Patients with digital subtraction angiography (DSA)-confirmed CNO were included. We collected information on clinical and demographic characteristics, carotid and transcranial ultrasonography and DSA findings, presence of full-collapse, collateral circulation, and cerebrovascular reactivity (CVR). RESULTS: One hundred thirty-five patients were analyzed. Ultrasonographic and DSA diagnosis of CNO were concordant in only 44%. This disagreement was related to the presence/absence of full-collapse: 45% of patients with CNO with full-collapse were classified as a complete carotid occlusion, and 40% with a CNO without full-collapse were interpreted as severe stenosis (p < 0.001). Mean velocities (mV) and pulsatility indexes (PIs) were significantly lower in the ipsilateral middle cerebral artery compared with the contralateral (43 cm/s vs 58 cm/s, p < 0.001; 0.80 vs 1.00, p < 0.001). Collateral circulation was identified in 92% of patients, with the anterior communicating artery (73%) being the most frequent. CVR was decreased or exhausted in 66% of cases and was more frequent in patients with a poor or absent collateral network compared with patients with ≥ 2 collateral arteries (82% vs 56%, p = 0.051). CONCLUSION: The accuracy of carotid ultrasonography in the diagnosis of CNO seems to be limited, with significant discrepancies with DSA. Decreased ipsilateral mV, PI, and CVR suggest a hemodynamic compromise in patients with CNO.
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Doenças das Artérias Carótidas , Estenose das Carótidas , Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Circulação Cerebrovascular , Circulação Colateral , Hemodinâmica , Humanos , Estudos Prospectivos , Sistema de Registros , Ultrassonografia Doppler TranscranianaRESUMO
Recent studies suggest that the ventral medial prefrontal cortex (vmPFC) encodes both operant drug self-administration and extinction memories. Here, we examined whether these opposing memories are encoded by distinct neuronal ensembles within the vmPFC with different outputs to the nucleus accumbens (NAc) in male and female rats. Using cocaine self-administration (3 h/d for 14 d) and extinction procedures, we demonstrated that vmPFC was similarly activated (indexed by Fos) during cocaine-seeking tests after 0 (no-extinction) or 7 extinction sessions. Selective Daun02 lesioning of the self-administration ensemble (no-extinction) decreased cocaine seeking, whereas Daun02 lesioning of the extinction ensemble increased cocaine seeking. Retrograde tracing with fluorescent cholera toxin subunit B injected into NAc combined with Fos colabeling in vmPFC indicated that vmPFC self-administration ensembles project to NAc core while extinction ensembles project to NAc shell. Functional disconnection experiments (Daun02 lesioning of vmPFC and acute dopamine D1-receptor blockade with SCH39166 in NAc core or shell) confirm that vmPFC ensembles interact with NAc core versus shell to play dissociable roles in cocaine self-administration versus extinction, respectively. Our results demonstrate that neuronal ensembles mediating cocaine self-administration and extinction comingle in vmPFC but have distinct outputs to the NAc core and shell that promote or inhibit cocaine seeking.SIGNIFICANCE STATEMENT Neuronal ensembles within the vmPFC have recently been shown to play a role in self-administration and extinction of food seeking. Here, we used the Daun02 chemogenetic inactivation procedure, which allows selective inhibition of neuronal ensembles identified by the activity marker Fos, to demonstrate that different ensembles for cocaine self-administration and extinction memories coexist in the ventral mPFC and interact with distinct subregions of the nucleus accumbens.
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Cocaína/administração & dosagem , Comportamento de Procura de Droga/fisiologia , Extinção Psicológica/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Animais , Condicionamento Operante/efeitos dos fármacos , Condicionamento Operante/fisiologia , Inibidores da Captação de Dopamina/administração & dosagem , Comportamento de Procura de Droga/efeitos dos fármacos , Extinção Psicológica/efeitos dos fármacos , Masculino , Rede Nervosa/química , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/fisiologia , Núcleo Accumbens/química , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/fisiologia , Córtex Pré-Frontal/química , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , Ratos Transgênicos , AutoadministraçãoRESUMO
PURPOSE OF REVIEW: The obesity epidemic is progressively affecting majority of individuals worldwide leading to many adverse metabolic and cardiovascular outcomes. Increasingly concerning among them is obesity hypertension (HTN). In this review, we delve into the physiology and therapeutic options in obesity HTN as we discuss the implications of obesity HTN on society. RECENT FINDINGS: Obesity is the most common cause of primary HTN and is directly proportional to increases BMI. The significance of adiposity in obesity HTN centers on humoral mechanisms via stimulation of the renal-angiotensin system, leptin activity, sympathetic overdrive, and proinflammatory processes that potentiate vascular remodeling, which results in a higher incidence of the progression of many known serious cardiovascular diseases. Although lifestyle and medical therapies have been recommended for obesity and its sequelae, continued global progression of this disease has driven the development of newer therapies such as carotid baroreflex activation therapy, renal denervation, and selective leptin receptor antagonism. SUMMARY: The pathophysiology of obesity HTN has not yet been fully elucidated despite it being one of the oldest known diseases to mankind. Major efforts to understand obesity HTN endures, paving opportunities for newer and possibly superior therapeutic options.
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Hipertensão/terapia , Sistema Nervoso Simpático , Barorreflexo , Humanos , Rim , Obesidade/terapiaRESUMO
BACKGROUND: Plasma exchange (PLEX) is a therapeutic option in the treatment of acute attacks of Demyelinating Diseases of the Central Nervous System (DDCNS). Factors related with PLEX response are not well established. METHODS: Descriptive and retrospective study. We included patients treated with PLEX for acute attacks of DDCNS between 2008 and 2017. We recorded demographics, clinical and treatment-related data, and Expanded Disability Status Scale (EDSS) score at admission, at discharge, and at 6 months. RESULTS: We included 64 patients. Forty-eight (75%) were female with a mean age of 48.28 ± 11.5 years. Half of our patients were diagnosed with multiple sclerosis. Clinical improvement was achieved in 51.6% at discharge and 62.5% at 6 months. The logistic regression model showed that EDSS score > 3 at admission (p = 0.04) and early clinical improvement with PLEX (p = 0.00) were predictors of good response to PLEX at discharge and at 6 months, respectively. No serious adverse effects were identified. CONCLUSIONS: PLEX is a safe and effective treatment for acute attacks of DDCNS. EDSS score at admission and early clinical improvement with PLEX were factors associated with good response to PLEX.
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Esclerose Múltipla , Neuromielite Óptica , Adulto , Sistema Nervoso Central , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/terapia , Neuromielite Óptica/terapia , Troca Plasmática , Estudos RetrospectivosRESUMO
BACKGROUND: Data on barriers and facilitators to prenatal oral health care among low-income US women are lacking. The objective of this study was to understand barriers/facilitators and patient-centered mitigation strategies related to the use of prenatal oral health care among underserved US women. METHODS: We used community-based participatory research to conduct two focus groups with eight pregnant/parenting women; ten individual in-depth interviews with medical providers, dental providers and community/social workers; and one community engagement studio with five representative community stakeholders in 2018-2019. Using an interpretive description research design, we conducted semi-structured interviews and focus groups which were audio-recorded, transcribed, and analyzed for thematic content. RESULTS: We identified individual and systemic barriers/facilitators to the utilization of prenatal oral health care by underserved US women. Strategies reported to improve utilization included healthcare system-wide changes to promote inter-professional collaborations, innovative educational programs to improve dissemination and implementation of prenatal oral health care guidelines, and specialized dental facilities providing prenatal oral health care to underserved women. Moreover, smartphones have the potential to be an innovative entry point to promote utilization of prenatal oral care at the individual level. CONCLUSIONS: Low-income women face multiple, addressable barriers to obtaining oral health care during pregnancy. Inter-professional collaboration holds strong promise for improving prenatal oral health care utilization.
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Aceitação pelo Paciente de Cuidados de Saúde , Smartphone , Feminino , Humanos , Gravidez , Gestantes , Cuidado Pré-Natal , Pesquisa QualitativaRESUMO
During 2014-2017, CDC Emerging Infections Program surveillance data reported that the occurrence of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections associated with injection drug use doubled among persons aged 18-49 years residing in Monroe County in western New York.* Unpublished surveillance data also indicate that an increasing proportion of all Candida spp. bloodstream infections in Monroe County and invasive group A Streptococcus (GAS) infections in 15 New York counties are also occurring among persons who inject drugs. In addition, across six surveillance sites nationwide, the proportion of invasive MRSA infections that occurred in persons who inject drugs increased from 4.1% of invasive MRSA cases in 2011 to 9.2% in 2016 (1). To better understand the types and frequency of these infections and identify prevention opportunities, CDC and public health partners conducted a rapid assessment of bacterial and fungal infections among persons who inject drugs in western New York. The goals were to assess which bacterial and fungal pathogens most often cause infections in persons who inject drugs, what proportion of persons who inject use opioids, and of these, how many were offered medication-assisted treatment for opioid use disorder. Medication-assisted treatment, which includes use of medications such as buprenorphine, methadone, and naltrexone, reduces cravings and has been reported to lower the risk for overdose death and all-cause mortality in persons who use opioids (2,3). In this assessment, nearly all persons with infections who injected drugs used opioids (97%), but half of inpatients (22 of 44) and 12 of 13 patients seen only in the emergency department (ED) were not offered medication-assisted treatment. The most commonly identified pathogen was S. aureus (80%), which is frequently found on skin. Health care visits for bacterial and fungal infections associated with injection opioid use are an opportunity to treat the underlying opioid use disorder with medication-assisted treatment. Routine care for patients who continue to inject should include advice on hand hygiene and not injecting into skin that has not been cleaned or to use any equipment contaminated by reuse, saliva, soil, or water (4,5).
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Infecções Bacterianas/epidemiologia , Micoses/epidemiologia , Vigilância da População , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Adulto JovemRESUMO
AIM: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. The phenotype of NAFLD varies widely, and non-invasive predictors of disease severity are scarce and are needed to tailor clinical management. METHODS: We compared liver fibrosis by histology with proposed non-invasive predictors of fibrosis, including alanine transaminase (ALT), aspartate transaminase (AST), AST/ALT ratio, AST to platelet ratio index, fibrosis-4, paediatric NAFLD fibrosis index and paediatric NAFLD fibrosis score. RESULTS: The area under the curve of scores obtained while predicting fibrosis in children with NAFLD ranged from 0.51 to 0.67. CONCLUSION: The tested non-invasive fibrosis scoring systems, some of which were originally designed for adult populations, did not adequately predict fibrosis in a paediatric cohort. Further development of risk prediction scores in children are needed for the management of paediatric patients and will likely need to be developed within a large paediatric data set in order to improve specificity and sensitivity.
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Cirrose Hepática/diagnóstico , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Adolescente , Área Sob a Curva , Criança , Feminino , Humanos , Fígado/metabolismo , Masculino , Auditoria Médica , Valor Preditivo dos Testes , Prognóstico , Estudos RetrospectivosRESUMO
UNLABELLED: In operant learning, initial reward-associated memories are thought to be distinct from subsequent extinction-associated memories. Memories formed during operant learning are thought to be stored in "neuronal ensembles." Thus, we hypothesize that different neuronal ensembles encode reward- and extinction-associated memories. Here, we examined prefrontal cortex neuronal ensembles involved in the recall of reward and extinction memories of food self-administration. We first trained rats to lever press for palatable food pellets for 7 d (1 h/d) and then exposed them to 0, 2, or 7 daily extinction sessions in which lever presses were not reinforced. Twenty-four hours after the last training or extinction session, we exposed the rats to either a short 15 min extinction test session or left them in their homecage (a control condition). We found maximal Fos (a neuronal activity marker) immunoreactivity in the ventral medial prefrontal cortex of rats that previously received 2 extinction sessions, suggesting that neuronal ensembles in this area encode extinction memories. We then used the Daun02 inactivation procedure to selectively disrupt ventral medial prefrontal cortex neuronal ensembles that were activated during the 15 min extinction session following 0 (no extinction) or 2 prior extinction sessions to determine the effects of inactivating the putative food reward and extinction ensembles, respectively, on subsequent nonreinforced food seeking 2 d later. Inactivation of the food reward ensembles decreased food seeking, whereas inactivation of the extinction ensembles increased food seeking. Our results indicate that distinct neuronal ensembles encoding operant reward and extinction memories intermingle within the same cortical area. SIGNIFICANCE STATEMENT: A current popular hypothesis is that neuronal ensembles in different prefrontal cortex areas control reward-associated versus extinction-associated memories: the dorsal medial prefrontal cortex (mPFC) promotes reward seeking, whereas the ventral mPFC inhibits reward seeking. In this paper, we use the Daun02 chemogenetic inactivation procedure to demonstrate that Fos-expressing neuronal ensembles mediating both food reward and extinction memories intermingle within the same ventral mPFC area.
Assuntos
Extinção Psicológica/fisiologia , Neurônios/metabolismo , Proteínas Oncogênicas v-fos/metabolismo , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/fisiologia , Recompensa , Animais , Condicionamento Operante/efeitos dos fármacos , Condicionamento Operante/fisiologia , Daunorrubicina/análogos & derivados , Daunorrubicina/farmacologia , Inibidores Enzimáticos/farmacologia , Extinção Psicológica/efeitos dos fármacos , GABAérgicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Masculino , Rememoração Mental/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fosfopiruvato Hidratase/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Ratos Long-Evans , Autoadministração , Fatores de Tempo , Proteína Vesicular 1 de Transporte de Glutamato/genética , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/genética , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismoRESUMO
OBJECTIVE: Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children. METHODS: This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD. Secondary outcomes compared hepatic copper levels against steatosis, fibrosis, lobular inflammation, balloon degeneration, and NAFLD activity score (NAS). RESULTS: The study analysis included 150 pediatric subjects (102 with NAFLD and 48 non-NAFLD). After adjusting for age, body mass index z score, gamma glutamyl transferase, alanine aminotransferase, and total bilirubin, NAFLD subjects had lower levels of hepatic copper than non-NAFLD (Pâ=â0.005). In addition, tissue copper concentration decreased as steatosis severity increased (Pâ<â0.001). Copper levels were not associated with degree of fibrosis, lobular inflammation, portal inflammation, or balloon degeneration. CONCLUSIONS: In this cohort of pediatric subjects with NAFLD, we observed decreased tissue copper levels in subjects with NAFLD when compared with non-NAFLD subjects. In addition, tissue copper levels were lower in subjects with nonalcoholic steatohepatitis, a more severe form of the disease, when compared with steatosis alone. Further studies are needed to explore the relationship between copper levels and NAFLD progression.
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Cobre/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Índice de Gravidade de Doença , Oligoelementos/metabolismo , Adolescente , Biomarcadores/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Estudos Retrospectivos , Adulto JovemRESUMO
N-methyl-D-aspartate receptors (NMDARs) are critically involved in various learning mechanisms including modulation of fear memory, brain development and brain disorders. While NMDARs mediate opposite effects on medial prefrontal cortex (mPFC) interneurons and excitatory neurons, NMDAR antagonists trigger profound cortical activation. The objectives of the present study were to determine the involvement of NMDARs expressed specifically in excitatory neurons in mPFC-dependent adaptive behaviors, specifically fear discrimination and fear extinction. To achieve this, we tested mice with locally deleted Grin1 gene encoding the obligatory NR1 subunit of the NMDAR from prefrontal CamKIIα positive neurons for their ability to distinguish frequency modulated (FM) tones in fear discrimination test. We demonstrated that NMDAR-dependent signaling in the mPFC is critical for effective fear discrimination following initial generalization of conditioned fear. While mice with deficient NMDARs in prefrontal excitatory neurons maintain normal responses to a dangerous fear-conditioned stimulus, they exhibit abnormal generalization decrement. These studies provide evidence that NMDAR-dependent neural signaling in the mPFC is a component of a neural mechanism for disambiguating the meaning of fear signals and supports discriminative fear learning by retaining proper gating information, viz. both dangerous and harmless cues. We also found that selective deletion of NMDARs from excitatory neurons in the mPFC leads to a deficit in fear extinction of auditory conditioned stimuli. These studies suggest that prefrontal NMDARs expressed in excitatory neurons are involved in adaptive behavior.
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Medo/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Estimulação Acústica , Animais , Percepção Auditiva/fisiologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Condicionamento Psicológico/fisiologia , Discriminação Psicológica/fisiologia , Extinção Psicológica/fisiologia , Feminino , Técnicas de Inativação de Genes , Generalização da Resposta/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo , Receptores de N-Metil-D-Aspartato/genéticaRESUMO
BACKGROUND: The United States Preventive Services Task Force (USPSTF) released updated guidelines in 2009 recommending aspirin to prevent myocardial infarction among at-risk men and stroke among at-risk women. OBJECTIVE: Our aim was to examine clinician aspirin recommendation among eligible persons based on cardiovascular risk scores and USPSTF cutoffs. DESIGN: We used across-sectional analysis of a current nationally representative sample. PARTICIPANTS: Participants were aged 40 years and older, and in the National Health and Nutrition Examination Survey (NHANES) (2011-2012). MAIN MEASURES: We determined aspirin eligibility for cardiovascular disease (CVD) prevention for each participant based on reported and assessed cardiovascular risk factors. We assessed men's risk using a published coronary heart disease risk calculator based on Framingham equations, and used a similar calculator for stroke to assess risk for women. We applied the USPSTF risk cutoffs for sex and age that account for offsetting risk for gastrointestinal hemorrhage. We assessed clinician recommendation for aspirin based on participant report. RESULTS: Among men 45-79 years and women 55-79 years, 87 % of men and 16 % of women were potentially eligible for primary CVD aspirin prevention. Clinician recommendation rates for aspirin among those eligible were low, 34 % for men and 42 % for women. Rates were highest among diabetics (63 %), those 65 to 79 years (52 %) or those in poor health (44 %). In contrast, aspirin recommendation rates were 76 % for CVD secondary prevention. After accounting for patient factors, particularly age, eligibility for aspirin prevention was not significantly associated with receiving a clinician's recommendation for aspirin (AOR 0.99 %; CI 0.7-1.4). CONCLUSIONS: Despite an "A recommendation" from the USPSTF for aspirin for primary prevention of CVD, the majority of men and women potentially eligible for aspirin did not recall a clinical recommendation from their clinician.
Assuntos
Aspirina/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Papel do Médico , Guias de Prática Clínica como Assunto , Prevenção Primária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais/métodos , Guias de Prática Clínica como Assunto/normas , Prevenção Primária/normasRESUMO
The preparticipation physical evaluation is a commonly requested medical visit for amateur and professional athletes of all ages. The overarching goal is to maximize the health of athletes and their safe participation in sports. Although studies have not found that the preparticipation physical evaluation prevents morbidity and mortality associated with sports, it may detect conditions that predispose the athlete to injury or illness and can provide strategies to prevent injuries. Clearance depends on the outcome of the evaluation and the type of sport (and sometimes position or event) in which the athlete participates. All persons undergoing a preparticipation physical evaluation should be questioned about exertional symptoms, presence of a heart murmur, symptoms of Marfan syndrome, and family history of premature serious cardiac conditions or sudden death. The physical examination should focus on the cardiovascular and musculoskeletal systems. U.S. medical and athletic organizations discourage screening electrocardiography and blood and urine testing in asymptomatic patients. Further evaluation should be considered for persons with heart or lung disease, bleeding disorders, musculoskeletal problems, history of concussion, or other neurologic disorders.
Assuntos
Saúde do Adolescente/normas , Atletas , Anamnese/normas , Exame Físico/normas , Esportes/normas , Adolescente , Humanos , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Anamnese/métodos , Exame Físico/métodos , Guias de Prática Clínica como Assunto , Estados UnidosRESUMO
BACKGROUND: Cancer screening rates are suboptimal for low-income patients. OBJECTIVE: To assess an intervention to increase cancer screening among patients in a safety-net primary care practice. DESIGN: Patients at an inner-city family practice who were overdue for cancer screening were randomized to intervention or usual care. Screening rates at 1 year were compared using the chi-square test, and multivariable analysis was performed to adjust for patient factors. SUBJECTS: All average-risk patients at an inner-city family practice overdue for mammography or colorectal cancer (CRC) screening. Patients' ages were 40 to 74 years (mean 53.9, SD 8.7) including 40.8 % African Americans, 4.2 % Latinos, 23.2 % with Medicaid and 10.9 % without any form of insurance. INTERVENTION: The 6-month intervention to promote cancer screening included letters, automated phone calls, prompts and a mailed Fecal Immunochemical Testing (FIT) Kit. MAIN MEASURES: Rates of cancer screening at 1 year. KEY RESULTS: Three hundred sixty-six patients overdue for screening were randomly assigned to intervention (n = 185) or usual care (n = 181). Primary analysis revealed significantly higher rates of cancer screening in intervention subjects: 29.7 % vs. 16.7 % for mammography (p = 0.034) and 37.7 % vs. 16.7 % for CRC screening (p = 0.0002). In the intervention group, 20 % of mammography screenings and 9.3 % of CRC screenings occurred at the early assessment, while the remainder occurred after repeated interventions. Within the CRC intervention group 44 % of screened patients used the mailed FIT kit. On multivariable analysis the CRC screening rates remained significantly higher in the intervention group, while the breast cancer screening rates were not statistically different. CONCLUSIONS: A multimodal intervention significantly increased CRC screening rates among patients in a safety-net primary care practice. These results suggest that relatively inexpensive letters and automated calls can be combined for a larger effect. Results also suggest that mailed screening kits may be a promising way to increase average-risk CRC screening.